Differences in nuclear triiodothyronine binding in rat brain cells suggest phylogenetic specialization of neuronal functions.

The central nervous system depends on thyroid hormones (TH) in regard to its development, maturation, and maintenance of normal functions. As there is much evidence to suggest that the effects of TH are mainly mediated through specific nuclear binding sites, we have studied the anatomical distribution of T3 nuclear receptors in different regions of adult rat brain, and the localization of receptors in the fractionated neuronal and glial nuclei of neocortex, paleocortex, and cerebellum. Purified nuclei from the various brain regions were prepared by ultracentrifugation in 2.2 M sucrose. Purified neuronal and glial fractions were obtained by discontinuous sucrose gradient centrifugation in 2.2 and 2.4 M sucrose. The washed nuclear fractions were used for T3 binding assay at 37 C for 30 min and the data analyzed by least squares nonlinear regression analysis. Nonfractionated nuclei from all regions studied were found to have similar dissociation constant (Kd) values (1.04-1.38 nM) and Eadie-Hofstee plots indicated the presence of an apparently ubiquitous single class of high affinity, low capacity binding sites. The increase in binding from cerebellum (54 +/- 24 fmol/mg DNA; mean +/- SE) to neocortex (666 +/- 89 fmol/mg DNA) showed a caudo-cranial pattern. In fractionated neuronal nuclei, the same trend was observed, only to a greater degree (1628 +/- 266, 994 +/- 76 and 212 +/- 29 fmol/mg DNA in neocortex, paleocortex, and cerebellum, respectively); the difference between corresponding values for glial nuclei of neocortex and paleocortex (357 +/- 139 and 250 +/- 92 fmol/mg DNA, respectively) was not statistically significant, and no specific T3 binding was found in cerebellar glial nuclei. These data suggest that TH may have an important role in neurons from phylogenetically newer regions, concerned with higher mental functions. The caudo-rostral distribution pattern may also indicate a gradient of TH actions in central nervous system regions.